title: The Bcl-2/Bax and Ras/Raf/MEK/ERK signaling pathways: implications in pediatric leukemia pathogenesis and new prospects for therapeutic approaches.
abstract: The Bcl-2/Bcl-xL/Bax and the Ras/Raf/MEK/ERK (MAPK) pathways are often deregulated in many human cancers and especially in acute lymphoblastic leukemia and acute myeloid leukemia. A result of molecular alterations of these pathways is uncontrolled cell growth and survival, ultimately resulting in oncogenic transformation and progression. Aberrant expression of Bcl-2/Bax and MAPK can lead to therapeutic resistance. In this review, the Bcl-2 and MAPK pathways are analyzed, focusing the attention on their molecular alterations, and the complex interactions between these signaling cascades are also analyzed. The observation that both MAPK and Bcl-2/Bax signaling play a central role in the pathogenesis of human cancer suggests that this kinase cascade represents a novel opportunity for the development of new anticancer targeted therapies designed to be less toxic than conventional chemotherapy. The evidence that they are often implicated in sensitivity and resistance to leukemia therapy suggests that characterization of the cancer genome may offer personalized cancer genomic information that can lead to the formulation of much more effective personalized therapy.
authors.affiliation: Pediatric Department, Pediatric Oncology Service, F Fede, II University of Naples, Naples, Italy.
authors.forename: Orsola
authors.initials: O
authors.lastname: Vitagliano
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Velia
authors.initials: V
authors.lastname: D'Angelo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Indolfi
authors.forename: Paolo
authors.initials: P
authors.lastname: Indolfi
authors.forename: Fiorina
authors.initials: F
authors.lastname: Casale
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D048490:raf Kinases / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)